Replication stress and resolution

1/21/22 SRH

Cancer cells replicate uncontrollably. And as such, they accumulate a lot of stalled replication forks and timing is key. This hot topic in our field is something that I think about a lot. What does the timing difference mean between forks that have stalled for a few hours and forks that have stalled for many hours? How does this change replication and repair mechanisms and outcomes?

For DNA Repair protein human RAD52, this can be the difference in proteins recruited, utilized, and repair mechanisms employed.

A new review has been published that really summarizes everything in our field in such a succinct way that I feel like I will read this paper several more times over the next coming months. It suggests that ssDNA gaps present within and surrounding the fork play an important role. This seems to be the case as has been highlighted by many groups including Sharon Cantor’s lab et al.

This paper has important implications under so many different contexts, I am trying to wrap my mind around everything.

Here is the paper:

Jackson LM, Moldovan GL. Mechanisms of PARP1 inhibitor resistance and their implications for cancer treatment. NAR Cancer. 2022 Dec 22;4(4):zcac042. doi: 10.1093/narcan/zcac042. PMID: 36568963; PMCID: PMC9773381.

If you study this phenomenon, here is a special collection calling for papers:

Communications Biology- a nature group is collecting publications for https://www.nature.com/collections/ebhjiebfhd